The Pilot Project Component is designed to provide a flexible means for developing and exploring new research activities or directions, and unique opportunities that can evolve into independently funded research projects. During Years 6-10 we propose funding two pilot projects per year with a budget of about $50,000 per project. The expected duration of these projects will be 1 year; projects can be extended to two years upon successful competitive renewal. The Center Scientific Director will manage this Component. Pilot Project applications will be solicited annually from EGCRC and UCSF investigators. Each proposal will be evaluated for scientific merit, innovation, and for relatedness to the Center's overall goals by at least two members of the ACTG Program Advisory Board, the Scientific Director, and the Center Director. Recommendations for funding will be considered for approval by the Center Steering Committee. Two Pilot Projects have been proposed and awarded funding for Year 06. Project 7A (A. Kayser, Director) will examine whether the Delta Opioid Receptor (DOR) agonist, ALK33, can be a potential drug to treat alcohol intake and craving in a preclinical human trial. Experiments in human subjects are also aimed to conducted fMRI studies to determine whether the increase the connectivity between the medial prefrontal cortex and brain regions associated with reward and anxiety. Project 7B (J. Wang, Director) is aimed to study whether excessive ethanol intake leads to the induction of AMPA receptor-mediated synaptic plasticity events in the dorsal striatum of rats by using a combination of slice electrophysiology and the state-of-the-art optogenetics approaches. The projects that were selected by the ACTG directors for funding during years 06. Both projects are expected to contribute to the overall goals of ACTG, which are identify and to validate novel targets for development of therapeutics for alcohol use disorders. The selected pilots will also add additional aspects to the Center (e.g., human clinical and imaging studies, and optogenetics)